PUS7通过调节GSPT1的Ψ修饰促进肝癌HepG2细胞增殖

PUS7 promotes hepatocellular carcinoma cell HepG2 proliferation by regulating Ψ-modification of GSPT1

目的 探讨PUS7促进肝癌HepG2细胞增殖的潜在机制。方法 根据TCGA数据库中肝癌数据集LIHC分析PUS7表达水平对肝癌患者的影响。敲低或过表达PUS7后,检测肝癌细胞HepG2的增殖能力。半定量蛋白质质谱以及遗传学操作鉴定PUS7影响肝癌细胞增殖的关键分子并分析其潜在机制。结果 低表达PUS7的肝癌患者较高表达患者具有较好的预后(P<0.05)。敲低PUS7后,肝癌细胞的增殖能力下降(P<0.05)、肝癌细胞中GSPT1的蛋白表达水平下降、肝癌细胞中GSPT1Ψ修饰下降(P<0.05);过表达PUS7后,肝癌细胞的增殖能力上升、肝癌细胞中GSPT1的蛋白表达水平上升、肝癌细胞中GSPT1Ψ修饰上升(P<0.05)。敲低GSPT1后,肝癌细胞增殖能力下降(P<0.05);过表达GSPT1后,肝癌细胞增殖能力上升(P<0.05)。PUS7敲除后肝癌细胞中GSPT1Ψ修饰下降(P<0.05)。在PUS7敲除细胞系中,过表达野生型PUS7后GSPT1Ψ修饰上升(P<0.05)。结论 PUS7通过调节GSPT1的Ψ修饰促进肝癌细胞HepG2增殖。

Aim To explore the potential mechanism of PUS7 promoting hepatoma HepG2 cell proliferation.Methods The effect of PUS7 expression level on hepatocellular carcinoma patients was analyzed according to the liver cancer dataset LIHC in TCGA database.The proliferation level of HepG2 in hepatocellular carcinoma cells was detected after knockdown or overexpression of PUS7.Semi-quantitative protein mass spectrometry as well as genetic manipulations were performed to identify key molecules of PUS7 affecting the proliferation level of hepatocellular carcinoma cells and analyze the underlying mechanisms.Results According to the expression level of PUS7 in hepatocellular carcinoma patients in TCGA database,it was found that hepatocellular carcinoma patients with low expression of PUS7 had better prognosis(P<0.05).The proliferation ability of hepatocellular carcinoma cells decreased after knockdown of PUS7,the protein expression level of GSPT1 decreased in hepatocellular carcinoma cells,and GSPT1Ψmodification decreased in hepatocellular carcinoma cells(P<0.05);the proliferation ability of hepatocellular carcinoma cells increased after overexpression of PUS7(P<0.05),the protein expression level of GSPT1 in hepatocellular carcinoma cells increased(P<0.05),and GSPT1Ψmodification in hepatocellular carcinoma cells increased(P<0.05).The proliferative capacity of hepatocellular carcinoma cells decreased after knockdown of GSPT1(P<0.05),and increased after overexpression of GSPT1(P<0.05).GSPT1Ψmodification was decreased in hepatocellular carcinoma cells after PUS7 knockdown(P<0.05).In PUS7 knockdown cell lines,GSPT1Ψmodification increased after overexpression of wild-type PUS7(P<0.05).Conclusion PUS7 promotes hepatocellular carcinoma cell HepG2 proliferation by regulating theΨmodification of GSPT1.